Research Topics
Genomes and Genes
| J C ReedSummaryAffiliation: The Burnham Institute Country: USA Publications
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Publications
Bc1-2, Raf-1 and mitochondrial regulation of apoptosisH G Wang
Burnham Institute, La Jolla, CA 92037, USA
Biofactors 8:13-6. 1998..The findings suggest that Bcl-2 targets Raf-1 to mitochondria, allowing this kinase to contribute to cellular survival by phosphorylating BAD or possibly other protein substrates in the vicinity of Bcl-2...
Bifunctional apoptosis inhibitor (BAR) protects neurons from diverse cell death pathwaysW Roth
The Burnham Institute, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
Cell Death Differ 10:1178-87. 2003..Taken together, the expression pattern and functional data suggest that the BAR protein is involved in the regulation of neuronal survival...
Drug insight: cancer therapy strategies based on restoration of endogenous cell death mechanismsJohn C Reed
Burnham Institute for Medical Research, La Jolla, CA 92037, USA
Nat Clin Pract Oncol 3:388-98. 2006..Several of the current strategies based on targeting core components of the cell death machinery for cancer therapy are reviewed here, and a summary of progress toward clinical applications is provided...
Cancer immunotherapy targeting survivin: commentary re: V. Pisarev et al., full-length dominant-negative survivin for cancer immunotherapy. Clin. Cancer Res., 9:6523-6533, 2003John C Reed
The Burnham Institute, La Jolla, California 92037, USA
Clin Cancer Res 9:6310-5. 2003
Apoptosis mechanisms: implications for cancer drug discoveryJohn C Reed
The Burnham Institute, La Jolla, California 92037, USA
Oncology (Williston Park) 18:11-20. 2004..Apoptosis-regulating genes are also beginning to find utility as targets for antisense oligonucleotides...
Bcl-2-family proteins and hematologic malignancies: history and future prospectsJohn C Reed
Burnham Institute for Medical Research, La Jolla, CA 92037, USA
Blood 111:3322-30. 2008..Experimental therapies targeting Bcl-2 family mRNAs or proteins are currently in clinical testing, raising hopes that a new class of anticancer drugs may be near...
Apoptosis-based therapies for hematologic malignanciesJohn C Reed
Burnham Institute, 10901 N Torrey Pines Rd, La Jolla, CA 92037, USA
Blood 106:408-18. 2005....
cIAP1 Localizes to the nuclear compartment and modulates the cell cycleTemesgen Samuel
Burnham Institute, La Jolla, CA 92037, USA
Cancer Res 65:210-8. 2005..Our findings demonstrate a role for overexpressed cIAP1 in genetic instability, possibly by interfering with mitotic functions of Survivin. These findings may have important implications for cancers in which cIAP1 overexpression occurs...
Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunitiesJ C Reed
Burnham Institute for Medical Research, La Jolla, CA 92037, USA
Cell Death Differ 13:1378-86. 2006....
A diverse family of proteins containing tumor necrosis factor receptor-associated factor domainsJ M Zapata
Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 276:24242-52. 2001..We propose the moniker TEFs (TD-encompassing factors) for this large family of proteins...
Regulation of Nur77 nuclear export by c-Jun N-terminal kinase and AktY H Han
Burnham Institute for Medical Research, Cancer Center, La Jolla, CA 92037, USA
Oncogene 25:2974-86. 2006..Together, our results demonstrate that both activation of JNK and inhibition of Akt play a role in translocation of Nur77 from the nucleus to the cytoplasm...
Microtubule-targeting drugs induce bcl-2 phosphorylation and association with Pin1N Pathan
The Burnham Institute, 10901 N Torrey Pines Rd, La Jolla, CA 92037, USA
Neoplasia 3:550-9. 2001....
TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosisE Leo
Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 276:8087-93. 2001..These data identify TRAF1 as a specific target of caspases activated during TNF- and Fas-induced apoptosis and illustrate differences in the repertoire of protease substrates cleaved during activation of different apoptotic pathways...
TUCAN, an antiapoptotic caspase-associated recruitment domain family protein overexpressed in cancerN Pathan
Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 276:32220-9. 2001..Thus, TUCAN represents a new member of the CARD family that selectively suppresses apoptosis induced via the mitochondrial pathway for caspase activation...
Bcl-B, a novel Bcl-2 family member that differentially binds and regulates Bax and BakN Ke
Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 276:12481-4. 2001..Bcl-B thus displays a unique pattern of selectivity for binding and regulating the function of other members of the Bcl-2 family...
CLAN, a novel human CED-4-like geneJ S Damiano
The Burnham Institute, La Jolla, California 92037, USA
Genomics 75:77-83. 2001..The CARD of the CLAN proteins binds a number of other CARD-containing proteins including caspase-1, BCL10, NOD2, and NAC. Once their physiologic functions are uncovered, CLAN proteins may prove to be valuable therapeutic targets...
The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspasesN Roy
The Burnham Institute, Program on Apoptosis and Cell Death Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
EMBO J 16:6914-25. 1997..Taken together, these findings suggest that c-IAP-1 and c-IAP-2 function similarly to XIAP by inhibiting the distal cell death proteases, caspases-3 and -7, whereas NAIP presumably inhibits apoptosis via other targets...
Structure-function analysis of Bag1 proteins. Effects on androgen receptor transcriptional activityD A Knee
Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 276:12718-24. 2001..Thus, both the unique NH(2)-terminal domain and the COOH-terminal Hsc70-binding domain of Bag1L are simultaneously required for its function as an AR regulator, whereas the conserved ubiquitin-like domain is expendable...
BAR: An apoptosis regulator at the intersection of caspases and Bcl-2 family proteinsH Zhang
Program on Apoptosis and Cell Death Regulation, The Burnham Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 97:2597-602. 2000..The BAR protein is anchored in intracellular membranes where Bcl-2 resides. BAR therefore may represent a scaffold protein capable of bridging two major apoptosis pathways...
IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugsI Tamm
The Burnham Institute, La Jolla, California 92037, USA
Cancer Res 58:5315-20. 1998..Although quantitative differences may exist, these observations suggest commonality in the mechanisms used by IAP-family proteins to suppress apoptosis...
IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspasesQ L Deveraux
The Burnham Institute, Program on Apoptosis and Cell Death Research, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
EMBO J 17:2215-23. 1998..These findings demonstrate that IAPs can suppress different apoptotic pathways by inhibiting distinct caspases and identify pro-caspase-9 as a new target for IAP-mediated inhibition of apoptosis...
Changes in intramitochondrial and cytosolic pH: early events that modulate caspase activation during apoptosisS Matsuyama
Programme on Apoptosis and Cell Death Regulation, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
Nat Cell Biol 2:318-25. 2000..These findings indicate that mitochondria-mediated alteration of intracellular pH may be an early event that regulates caspase activation in the mitochondrial pathway for apoptosis...
Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responsesS I Matsuzawa
The Burnham Institute, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
Mol Cell 7:915-26. 2001..Expression of Siah is induced by p53, revealing a way of linking genotoxic injury to destruction of beta-catenin, thus reducing activity of Tcf/LEF transcription factors and contributing to cell cycle arrest...
Dynamics of expression of apoptosis-regulatory proteins Bid, Bcl-2, Bcl-X, Bax and Bak during development of murine nervous systemM Krajewska
The Burnham Institute, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
Cell Death Differ 9:145-57. 2002..Among the Bcl-2 family proteins only Bid and Bcl-XL continue to be expressed at high levels in the adult brain...
Ca2+-induced apoptosis through calcineurin dephosphorylation of BADH G Wang
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Science 284:339-43. 1999..Thus, a Ca2+-inducible mechanism for apoptosis induction operates by regulating BAD phosphorylation and localization in cells...
Structural analysis of BAG1 cochaperone and its interactions with Hsc70 heat shock proteinK Briknarová
The Burnham Institute, La Jolla, California 92037, USA
Nat Struct Biol 8:349-52. 2001..The results provide a structural basis for understanding the mechanism by which BAG proteins link molecular chaperones and cell signaling pathways...
Immunohistochemical analysis of in vivo patterns of expression of CPP32 (Caspase-3), a cell death proteaseM Krajewska
Apoptosis and Cell Death Research Program, The Burnham Institute, La Jolla, California 92037, USA
Cancer Res 57:1605-13. 1997..These findings establish for the first time the cell type- and differentiation-specific patterns of expression of an interleukin-1beta converting enzyme/CED-3 (Caspase) family protease...
Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemiaS Krajewski
The Burnham Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 96:5752-7. 1999..Loss of mitochondrial barrier function during neuronal damage from ischemia or other insults therefore may play an important role in making certain caspases available to participate in apoptosis...
Bax inhibitor-1, a mammalian apoptosis suppressor identified by functional screening in yeastQ Xu
Burnham Institute Program on Apoptosis and Cell Death Research La Jolla, California 92037, USA
Mol Cell 1:337-46. 1998..Conversely, BI-1 antisense induced apoptosis. BI-1 thus represents a new type of regulator of cell death pathways controlled by Bcl-2 and Bax...
Expression and location of Hsp70/Hsc-binding anti-apoptotic protein BAG-1 and its variants in normal tissues and tumor cell linesS Takayama
The Burnham Institute, La Jolla, California 92037, USA
Cancer Res 58:3116-31. 1998....
The carboxyl-terminal lobe of Hsc70 ATPase domain is sufficient for binding to BAG1L Brive
The Burnham Institute, 10901 N Torrey Pines Road, La Jolla, California 92037, USA
Biochem Biophys Res Commun 289:1099-105. 2001..This result suggests that the stabilizing contacts for docking of BAG1 to Hsc70 are located in the C-terminal lobe of the ATPase domain. These findings provide new insights into the role of co-chaperones as nucleotide exchange factors...
Regulation of cell death protease caspase-9 by phosphorylationM H Cardone
Program on Apoptosis and Cell Death Research, The Burnham Institute, La Jolla, CA 92037, USA
Science 282:1318-21. 1998..Mutant pro-Casp9(Ser196Ala) was resistant to Akt-mediated phosphorylation and inhibition in vitro and in cells, resulting in Akt-resistant induction of apoptosis. Thus, caspases can be directly regulated by protein phosphorylation...
BIRinging chromosomes through cell division--and survivin' the experienceJ C Reed
The Burnham Institute, La Jolla, California 92037, USA
Cell 102:545-8. 2000
A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteinsT Miyazaki
The Burnham Institute, 10901 N Torrey Pines Rd, La Jolla, CA 92037, USA
Nat Immunol 2:493-500. 2001..Elucidation of this mechanism suggests GTP-binding proteins as potential targets for pharmacological intervention in TRAIL-induced apoptosis...
Microtubule-targeting drugs induce Bcl-2 phosphorylation and association with Pin1N Pathan
The Burnham Institute, 10901 N Torrey Pines, La Jolla, CA 92037, USA
Neoplasia 3:70-9. 2001....
p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1S Matsuzawa
Burnham Institute, La Jolla, CA 92037, USA
EMBO J 17:2736-47. 1998..We suggest that Siah-1A may be an important mediator of p53-dependent cell-cycle arrest and demonstrate that Siah-1A is directly inhibited by BAG-1...
TNFR-associated factor family protein expression in normal tissues and lymphoid malignanciesJ M Zapata
The Burnham Institute, Program on Apoptosis and Cell Death Regulation, La Jolla, California 92037, USA
J Immunol 165:5084-96. 2000..01), as determined by immunoblotting. These findings contribute to an improved understanding of the cell-specific roles of TRAFs in normal tissues and provide evidence of altered TRAF1 expression in lymphoid malignancies...
Bcl-2 family proteins and mitochondriaJ C Reed
The Burnham Institute, Program on Apoptosis and Cell Death Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Biochim Biophys Acta 1366:127-37. 1998....
An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulatorsS Takayama
The Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 274:781-6. 1999..The findings suggest opportunities for specification and diversification of Hsp70/Hsc70 chaperone functions through interactions with various BAG-family proteins...
A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosisZ L Chu
Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 276:9239-45. 2001..NAC expression in vivo is associated with terminal differentiation of short lived cells in epithelia and some other tissues. The ability of NAC to enhance Apaf1-apoptosome function reveals a novel paradigm for apoptosis regulation...
TRAF2-binding BIR1 domain of c-IAP2/MALT1 fusion protein is essential for activation of NF-kappaBJ B Garrison
Program on Apoptosis and Cell Death Research, Cancer Center, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
Oncogene 28:1584-93. 2009....
Bag1 is a regulator and marker of neuronal differentiationP Kermer
The Burnham Institute, Program on Apoptosis and Cell Death Research, 10901 N Torrey Pines Road, La Jolla, California, CA 92037, USA
Cell Death Differ 9:405-13. 2002..Taken together, these findings raise the possibility that the Bag1 protein is expressed early in neurogenesis in vivo and is capable of modulating neuronal cell survival and differentiation at least in part from a nuclear location...
Thymidine-phosphorothioate oligonucleotides induce activation and apoptosis of CLL cells independently of CpG motifs or BCL-2 gene interferenceJ E Castro
John and Rebecca Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
Leukemia 20:680-8. 2006..We conclude that thymidine-containing PS-ODN can activate CLL cells and induce apoptosis via a mechanism that is independent of BCL-2 gene interference or CpG motifs...
Drosophila pro-apoptotic Bcl-2/Bax homologue reveals evolutionary conservation of cell death mechanismsH Zhang
Program on Apoptosis and Cell Death Regulation, Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 275:27303-6. 2000..Moreover, DBok targets mitochondria and triggers cytochrome c release through a caspase-independent mechanism. These characteristics of DBok reveal evolutionary conservation of cell death mechanisms in flies and humans...
Characterization of interactions between the anti-apoptotic protein BAG-1 and Hsc70 molecular chaperonesJ K Stuart
Burnham Institute, Cancer Research Center, La Jolla, California 92037, USA
J Biol Chem 273:22506-14. 1998..Molecular modeling permitted a comparison of structural features between the functionally homologous BAG-1 and GrpE proteins. These data were used to propose a mechanism for BAG-1 in the regulation of Hsp70/Hsc70 chaperone activity...
Bcl-G, a novel pro-apoptotic member of the Bcl-2 familyB Guo
Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 276:2780-5. 2001..A mutant of Bcl-G(L) in which the BH2 domain was deleted displayed increased apoptotic activity and coimmunoprecipitated with Bcl-X(L), suggesting that the BH2 domain autorepresses Bcl-G(L)...
Bax directly induces release of cytochrome c from isolated mitochondriaJ M Jurgensmeier
Program on Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 95:4997-5002. 1998....
Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3H Li
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Science 289:1159-64. 2000..Our results reveal a mechanism by which a nuclear transcription factor translocates to mitochondria to initiate apoptosis...
BAG1L enhances trans-activation function of the vitamin D receptorM Guzey
Burnham Institute, La Jolla, California 92037 and RIGEB, MAM TUBITAK, P K 21 Gebze 41 470, Kocaeli, Turkey
J Biol Chem 275:40749-56. 2000..Thus, BAG1L is a direct regulator of VDR, which enhances its trans-activation function and improves tumor cell responses to growth-suppressive VDR ligands...
A single BIR domain of XIAP sufficient for inhibiting caspasesR Takahashi
Burnham Institute, Program on Apoptosis and Cell Death Regulation, La Jolla, California 92037, USA
J Biol Chem 273:7787-90. 1998..These findings identify BIR2 as the minimal caspase-inhibitory domain of XIAP and indicate that a single BIR domain can be sufficient for binding and inhibiting caspases...
TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis inductionX Ye
The Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 274:30202-8. 1999..These results demonstrate that TRAF family proteins interact with p75(NTR) and differentially modulate its NF-kappaB activation and cell death induction...
The Drosophila tumor necrosis factor receptor-associated factor-1 (DTRAF1) interacts with Pelle and regulates NFkappaB activityJ M Zapata
The Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 275:12102-7. 2000..Interactions of DTRAF1 with human TRAF-, TNF receptor-, and IAP-family proteins imply strong evolutionary conservation of TRAF protein structure and function throughout Metazoan evolution...
A short Nur77-derived peptide converts Bcl-2 from a protector to a killerSiva Kumar Kolluri
Cancer Center, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
Cancer Cell 14:285-98. 2008..NuBCP-9s act as molecular switches to dislodge the Bcl-2 BH4 domain, exposing its BH3 domain, which in turn blocks the activity of antiapoptotic Bcl-X(L)...
Discovery, characterization, and structure-activity relationships studies of proapoptotic polyphenols targeting B-cell lymphocyte/leukemia-2 proteinsShinichi Kitada
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
J Med Chem 46:4259-64. 2003....
An inducible pathway for degradation of FLIP protein sensitizes tumor cells to TRAIL-induced apoptosisYoungsoo Kim
Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 277:22320-9. 2002....
Expression and potential role of Fas-associated phosphatase-1 in ovarian cancerI Meinhold-Heerlein
Program on Apoptosis and Cell Death Research, The Burnham Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA
Am J Pathol 158:1335-44. 2001..We conclude that FAP-1 correlates significantly with Fas resistance in ovarian cancer cell lines and is commonly expressed in ovarian cancers...
Molecular basis for CD40 signaling mediated by TRAF3C Z Ni
Cancer Center, The Burnham Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 97:10395-9. 2000..TRAF2 suggests that CD40 may assume different conformations when bound to different TRAF family members. This molecular adaptation may influence binding affinity and specific cellular triggers...
TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissuesM Krajewska
Burnham Institute, La Jolla, CA 92037, USA
Am J Pathol 152:1549-61. 1998..Although also expressed in some types of mesenchymal cells, these findings suggest that TRAF-4 is a marker of normal epithelial stem cells, the expression of which often ceases on differentiation and malignant transformation...
Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic acid-induced apoptosis in cancer cellsR Liu
The Burnham Institute, Cancer Research Center, La Jolla, California 92037, USA
J Biol Chem 273:16985-92. 1998..These results demonstrate that BAG-1 can regulate retinoid activities through its interaction with RAR and suggest that elevated levels of BAG-1 protein could potentially contribute to retinoid resistance in cancer cells...
Developmental expression patterns of Bcl-2, Bcl-x, Bax, and Bak in teethS Krajewski
The Burnham Institute formerly La Jolla Cancer Research Foundation, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Cell Death Differ 5:408-15. 1998....
BAG-1L protein enhances androgen receptor functionB A Froesch
Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 273:11660-6. 1998..These findings implicate BAG-1L in the regulation of AR function and may have relevance to mechanisms of prostate cancer resistance to hormone-ablative and anti-androgen therapy...
Mechanisms of apoptosisJ C Reed
Burnham Institute, La Jolla, California 92037, USA
Am J Pathol 157:1415-30. 2000..Knowledge of the molecular mechanisms of apoptosis is providing insights into the causes of multiple pathologies where aberrant cell death regulation occurs and is beginning to provide new approaches to the treatment of human diseases...
Bcl-2 family proteinsJ C Reed
The Burnham Institute, La Jolla, California 92037, USA
Oncogene 17:3225-36. 1998....
X-linked IAP is a direct inhibitor of cell-death proteasesQ L Deveraux
The Burnham Institute, Program on Apoptosis and Cell Death Research, La Jolla, California 92037, USA
Nature 388:300-4. 1997....
Synthetic triterpenoids activate a pathway for apoptosis in AML cells involving downregulation of FLIP and sensitization to TRAILW-S Suh
The Burnham Institute, La Jolla, CA 92037, USA
Leukemia 17:2122-9. 2003..The findings suggest that synthetic triterpenoids warrant further investigation in the treatment of AML, alone or in combination with TRAIL or other immune-based therapies...
PAAD - a new protein domain associated with apoptosis, cancer and autoimmune diseasesK Pawłowski
Program in Bioinformatics and Biological Complexity, The Burnham Institute, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
Trends Biochem Sci 26:85-7. 2001..Its location within these proteins and predicted fold suggests that it functions as a protein-protein interaction domain, possibly uniting different signaling pathways...
Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3Bingzhen Lin
The Burnham Institute, Cancer Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Cell 116:527-40. 2004....
Apoptosis-regulating proteins as targets for drug discoveryJ C Reed
The Burnham Institute, La Jolla, CA 92037, USA
Trends Mol Med 7:314-9. 2001....
BAG-1 modulates the chaperone activity of Hsp70/Hsc70S Takayama
The Burnham Institute, Program on Apoptosis and Cell Death Research, La Jolla, CA 92037, USA
EMBO J 16:4887-96. 1997..The inhibitory effects of BAG-1 on Hsp/Hsc70 chaperone activity suggest that BAG-1 represents a novel type of chaperone regulatory proteins and thus suggest a link between cell signaling, cell death and the stress response...
HBXIP functions as a cofactor of survivin in apoptosis suppressionHiroyuki Marusawa
The Burnham Institute, La Jolla, CA 92037, USA
EMBO J 22:2729-40. 2003..Thus, HBXIP functions as a cofactor for survivin, and serves as a link between the cellular apoptosis machinery and a viral pathogen involved in hepatocellular carcinogenesis...
Identification of small molecules that sensitize resistant tumor cells to tumor necrosis factor-family death receptorsAaron D Schimmer
Burnham Institute for Medical Research, La Jolla, California 92037, USA
Cancer Res 66:2367-75. 2006....
Triterpenoids display single agent anti-tumor activity in a transgenic mouse model of chronic lymphocytic leukemia and small B cell lymphomaChristina L Kress
Burnham Institute for Medical Research, La Jolla, California, United States of America
PLoS ONE 2:e559. 2007..In this report, we have studied the effects of CDDO and its imidazolide derivative (CDDO-Im) on chronic lymphocytic leukemia (CLL), using patients' CLL cells and a mouse model of CLL and small B cell lymphoma (SBL)...
Cellular, biochemical, and genetic analysis of mechanism of small molecule IAP inhibitorsZhiliang Wang
The Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 279:48168-76. 2004....
Apoptosis-associated speck-like protein containing a caspase recruitment domain is a regulator of procaspase-1 activationChristian Stehlik
Burnham Institute, La Jolla, CA 92037, USA
J Immunol 171:6154-63. 2003....
Structurally distinct recognition motifs in lymphotoxin-beta receptor and CD40 for tumor necrosis factor receptor-associated factor (TRAF)-mediated signalingChenglong Li
Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 278:50523-9. 2003..The results reveal structurally adaptive "hot spots" in the TRAF3-binding crevice that promote molecular interactions driving specific signaling after contact with LTbetaR, CD40, or the downstream regulator TANK...
Functional role of death-associated protein 3 (DAP3) in anoikisTadaaki Miyazaki
The Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 279:44667-72. 2004..Involvement of DAP3 in anoikis signaling demonstrates a novel role for this GTP-binding protein in apoptosis induction caused by cell detachment...
Apogossypol derivatives as antagonists of antiapoptotic Bcl-2 family proteinsJun Wei
Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 90237, USA
Mol Cancer Ther 8:904-13. 2009..Together with its improved plasma and microsomal stability relative to Apogossypol, BI79D10 represents a lead compound for the development of novel apoptosis-based therapies for cancer...
Cytoprotective peptide humanin binds and inhibits proapoptotic Bcl-2/Bax family protein BimELFrederic Luciano
The Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 280:15825-35. 2005..Taken together, our results indicate that the inhibition of BimEL may contribute to the antiapoptotic properties of the HN peptide...
Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunitiesInKi Kim
Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
Nat Rev Drug Discov 7:1013-30. 2008....
CADD, a Chlamydia protein that interacts with death receptorsFrank Stenner-Liewen
Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 277:9633-6. 2002..trachomatis and co-localizes with Fas in the proximity of the inclusion body. The results suggest a role for CADD modulating the apoptosis pathways of cells infected, revealing a new mechanism of host-pathogen interaction...
Distinct BIR domains of cIAP1 mediate binding to and ubiquitination of tumor necrosis factor receptor-associated factor 2 and second mitochondrial activator of caspasesTemesgen Samuel
Burnham Institute for Medical Research, La Jolla, CA 92037, USA
J Biol Chem 281:1080-90. 2006....
Gambogic acid is an antagonist of antiapoptotic Bcl-2 family proteinsDayong Zhai
Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Mol Cancer Ther 7:1639-46. 2008..Altogether, the findings suggest that suppression of antiapoptotic Bcl-2 family proteins may be among the cytotoxic mechanisms by which GA kills tumor cells...
Bcl-2 antagonist apogossypol (NSC736630) displays single-agent activity in Bcl-2-transgenic mice and has superior efficacy with less toxicity compared with gossypol (NSC19048)Shinichi Kitada
Burnham Institute for Medical Research, Cancer Research Center, La Jolla, CA 92037, USA
Blood 111:3211-9. 2008..Taken together, these studies indicate that apogossypol is superior to parent compound gossypol with respect to toxicology and efficacy, suggesting that further development of this compound for cancer therapy is warranted...
Synthesis and biological evaluation of Apogossypolone derivatives as pan-active inhibitors of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteinsJun Wei
Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
J Med Chem 53:8000-11. 2010..Together with its negligible toxicity, compound 6f represents a promising drug lead for the development of novel apoptosis-based therapies for cancer...
ZIP kinase triggers apoptosis from nuclear PML oncogenic domainsTaro Kawai
The Burnham Institute, La Jolla, California 92037, USA
Mol Cell Biol 23:6174-86. 2003..These results suggest that ZIPK, in collaboration with Daxx and Par-4, mediates a novel nuclear pathway for apoptosis...
Vaccinia virus virulence factor N1L is a novel promising target for antiviral therapeutic interventionAnton V Cheltsov
Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA
J Med Chem 53:3899-906. 2010..We have also identified the natural polyphenol resveratrol as a moderate N1L inhibitor. Finally, we show that our ligands efficiently inhibit growth of vaccinia virus...
Elevated expression of inhibitor of apoptosis proteins in prostate cancerMaryla Krajewska
The Burnham Institute, La Jolla, California 92037, USA
Clin Cancer Res 9:4914-25. 2003..CONCLUSIONS: The findings demonstrate that tumor- associated elevations in the expression of several IAP family proteins occur as a frequent and early event in the etiology of prostate cancer...
Vaccinia virus protein F1L is a caspase-9 inhibitorDayong Zhai
Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
J Biol Chem 285:5569-80. 2010....
Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activityAaron D Schimmer
The Burnham Institute, La Jolla, CA 92037, USA
Cancer Cell 5:25-35. 2004..Active compounds also suppressed growth of established tumors in xenograft models in mice, while displaying little toxicity to normal tissues. These findings validate IAPs as targets for cancer drug discovery...
Nur77 converts phenotype of Bcl-B, an antiapoptotic protein expressed in plasma cells and myelomaFrederic Luciano
Burnham Institute for Medical Research, 10901 Torrey Pines Road, La Jolla, CA 92037, USA
Blood 109:3849-55. 2007..Because Bcl-B is abundantly expressed in plasma cells and some myelomas, these findings raise the possibility of exploiting the Nur77/Bcl-B mechanism for apoptosis for eradication of autoimmune plasma cells or myeloma...
Peptides targeting caspase inhibitorsIngo Tamm
The Burnham Institute, La Jolla, California 97037, USA
J Biol Chem 278:14401-5. 2003..Peptides interacting with XIAP could serve as prototypes for the design of low molecular weight modulators of apoptosis...
Apoptosis induction by 1alpha,25-dihydroxyvitamin D3 in prostate cancerMeral Guzey
Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA
Mol Cancer Ther 1:667-77. 2002..Thus, VD3 is capable of inhibiting expression of multiple antiapoptotic proteins in VDR-expressing prostate cancer cells, leading to activation of the mitochondrial pathway for apoptosis...
The PAAD/PYRIN-family protein ASC is a dual regulator of a conserved step in nuclear factor kappaB activation pathwaysChristian Stehlik
The Burnham Institute, The Scripps Research Institute, La Jolla, CA 92037, USA
J Exp Med 196:1605-15. 2002..Our findings suggest that ASC modulates diverse NF-kappaB induction pathways by acting upon the IKK complex, implying a broad role for this and similar proteins containing PAAD domains in regulation of inflammatory responses...
Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemiaPeter Chu
The Chronic Lymphocytic Leukemia Research Consortium, Biomedical Sciences Graduate Program, Division of Hematology Oncology, Stein Institute for Research on Aging, School of Medicine, University of California at San Diego, La Jolla, CA 92093 0663, USA
Proc Natl Acad Sci U S A 99:3854-9. 2002....
Identification and characterization of DEDD2, a death effector domain-containing proteinWilfried Roth
The Burnham Institute, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
J Biol Chem 277:7501-8. 2002..These findings suggest that DEDD2 is involved in the regulation of nuclear events mediated by the extrinsic apoptosis pathway...
Functional blocks in caspase activation pathways are common in leukemia and predict patient response to induction chemotherapyAaron D Schimmer
The Burnham Institute, La Jolla, California 92037, USA
Cancer Res 63:1242-8. 2003..This study supports the importance of apoptosis pathways in determining response to chemotherapy and suggests that functional defects in caspase activation are prognostic in patients with leukemia...
Bag1 proteins regulate growth and survival of ZR-75-1 human breast cancer cellsMasafumi Kudoh
The Burnham Institute, La Jolla, California 92037, USA
Cancer Res 62:1904-9. 2002..Altogether, these findings demonstrate that Bag1 and Bag1L provoke similar changes in breast cancer cell growth and survival and suggest that interference with Bag1 or Bag1L function might be a useful strategy for opposing breast cancer...
Fragment-based design of small molecule X-linked inhibitor of apoptosis protein inhibitorsJui Wen Huang
Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
J Med Chem 51:7111-8. 2008..Hence, as an application, we report on the derivation of novel, selective, druglike, cell permeable SMAC mimics with cellular activity...
Conformation of membrane-associated proapoptotic tBidXiao Min Gong
Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 279:28954-60. 2004....
Synthetic triterpenoids cooperate with tumor necrosis factor-related apoptosis-inducing ligand to induce apoptosis of breast cancer cellsMarc L Hyer
The Burnham Institute, La Jolla, California 92037, USA
Cancer Res 65:4799-808. 2005..These data suggest that CDDO and CDDO-Im may be useful for selectively reversing the TRAIL-resistant phenotype in cancer but not normal cells...
Key molecular contacts promote recognition of the BAFF receptor by TNF receptor-associated factor 3: implications for intracellular signaling regulationChao Zhou Ni
Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA
J Immunol 173:7394-400. 2004..The structure of the complex provides a molecular explanation for binding affinities and selective protein interactions in TNFR-TRAF interactions...
Research Grants
- MITOCHONDRIA AND APOPTOSISJohn Reed; Fiscal Year: 2007....
- Yeast-based HTS Assay Technologies for ProteasesJohn Reed; Fiscal Year: 2009..For proof of concept, we focus on proteases important for inflammatory and infectious diseases. ..
- Chemical Antagonists of IAP-Family Anti-Apoptotic ProteinsJohn Reed; Fiscal Year: 2007..The resulting compounds will be useful as research tools for understanding the biology of IAPs and for ascertaining their roles in diseases such as cancer, where IAP over-expression is commonly observed. ..
- SIGNAL TRANSDUCTION AND CELL DEATH REGULATIONJohn Reed; Fiscal Year: 2007....
- Apoptosis-Based Cancer Drug DiscoveryJohn Reed; Fiscal Year: 2007..This knowledge-base can now be exploited for devising strategies for small molecule drug discovery, towards the goal of revolutionary new treatments for cancer and leukemia. ..
- Mechanisms of the HBX-interacting protein (HBXIP)John Reed; Fiscal Year: 2007..Altogether, these investigations will define the role of HBXIP in regulating cell division and apoptosis, as well as providing new insights into the mechanisms of HBx in the pathogenesis of HCC. ..
- PAAD-Family Proteins and Host Defense MechanismsJohn Reed; Fiscal Year: 2007..abstract_text> ..
- Chemical Inhibitors of ER StressJohn Reed; Fiscal Year: 2007....
- NLR Family Proteins: Mechanisms and RegulationJohn Reed; Fiscal Year: 2009..Thus, studies of NLRs have relevance to a wide diversity of human diseases. ..
- BI-1, A Regulator of ER-Stress Pathways Linked to ApoptosisJohn Reed; Fiscal Year: 2009..Altogether, these studies will improve understanding of how damage to the ER is linked to apoptosis, and will potentially reveal strategies for neuronal preservation in stroke and neurodegenerative diseases. ..
- Mitochondria and Apoptosis (revised GM60554)John Reed; Fiscal Year: 2009..abstract_text> ..
- BAG-1--A NOVEL BCL-2 BINDING PROTEINJohn Reed; Fiscal Year: 1999....
- BAX INHIBITORY PROTEINS, BI1 AND BI2John Reed; Fiscal Year: 2002....
- CED-4 FAMILY PROTEINSJohn Reed; Fiscal Year: 2003..The information provided by these investigations may provide insights into human diseases where dysregulation of programmed cell death is known to occur and may lead to new strategies for therapeutic intervention. ..
- MITOCHONDRIA AND APOPTOSISJohn Reed; Fiscal Year: 2003..g. myocardial infarction, stroke; AIDS; neurodegeneration), the insights gains from these investigations could find broad applicability to the improved treatment of several human diseases. ..
